Many toxic xenobiotics appear to be either strong electrophiles or capable of producing strong electrophiles in the body. The reaction of these electrophiles with critical body nucleophiles triggers the sequence of biochemical changes which ultimately produce tissue damage. Conjugation with glutathione represents the body's first line of defense against toxic electrophiles. The glutathione S-transferases are the enzymes which are responsible for catalyzing these reactions and hence play a key role in the protection of tissues against damage by electrophiles. The objective of the proposed studies is to examine in a systematic fashion the stereochemical aspects and mechanisms of some of the conjugation features of foreign compounds which enhance their ability to act as substrates for these enzymes. We will examine the stereochemical aspects of the conjugation of Beta-methyl styrene oxide isomers and the substitution reactions of l-substituted ethyl benzenes and 2-substituted octanes catalyzed by rat liver glutathione S-transferase isozymes. We will also examine the stereochemical aspects of the metabolism of l-chloroethyl benzene in vivo.